title: Frequent reduction of gap junctional intercellular communication and connexin43 expression in human and mouse lung carcinoma cells.
abstract: The reduced gap junctional intercellular communication (GJIC) and gap junction protein (connexin) expression that have been noted in many neoplastic cell types may contribute to the neoplastic phenotype. We assessed GJIC (by fluorescent dye micro-injection) and connexin expression (by Northern blotting, Western blotting and immunohistochemistry) in five mouse and 17 human lung carcinoma cell lines; both measures were lower in neoplastic cells compared to non-transformed lung epithelial cells. Other connexins were not detected in these cells. Co-culture experiments indicated that carcinoma cell lines able to transfer dye among themselves (homologous GJIC) had little capacity for dye-coupling with non-transformed cells (heterologous GJIC). Southern blot analyses indicated that reductions in GJIC and connexin43 expression were not due to deletions or rearrangements of this gene, but were more likely accounted for by transcriptional down-regulation and/or post-transcriptional factors. No correlations between GJIC and known oncogene and tumor suppressor gene alterations in the human lung carcinoma cells were apparent, suggesting that other mechanisms down-regulate GJIC in these cells. Since the neoplastic cell lines exhibited low GJIC (either homologous or heterologous), this characteristic may be involved in expression of the neoplastic phenotype.
authors.affiliation: Department of Pathology, Medical College of Ohio, Toledo 43699, USA.
authors.forename: K
authors.initials: K
authors.lastname: Cesen-Cummings
authors.forename: M J
authors.initials: MJ
authors.lastname: Fernstrom
authors.forename: A M
authors.initials: AM
authors.lastname: Malkinson
authors.forename: R J
authors.initials: RJ
authors.lastname: Ruch
mesh_terms: D000230:Adenocarcinoma / Q000503:physiopathology; D000818:Animals; D018287:Carcinoma, Large Cell / Q000503:physiopathology; D018288:Carcinoma, Small Cell / Q000503:physiopathology; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology; D002450:Cell Communication / Q000502:physiology*; D002461:Cell Line, Transformed; D018031:Connexin 43 / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000502:physiology; D019084:Fluorescent Antibody Technique, Indirect; D017629:Gap Junctions / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000502:physiology*; D008175:Lung Neoplasms / Q000503:physiopathology*; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D018031:Connexin 43; D012333:RNA, Messenger